Gastric cancer remains the third most common cause of cancer-related death worldwide.
Two different pathogeneses of gastric cancer have been proposed, correlating to two histologic types: intestinal and diffuse.
Gastrectomy is the recommended treatment in relatively early localized gastric cancer (T1b); however, in more advanced gastric cancers (T2N0, T1aN+, or T1b-T3N+), adjunctive therapy in addition to gastrectomy is recommended.
The results of INT-0116 study (adjuvant chemoradiation) and Medical Research Council ST02/MAGIC and the FLOT study (perioperative chemotherapy) have shaped the current practice of resectable gastric cancer treatment in Western countries.
In Asia, postoperative chemotherapy has been considered standard after gastrectomy with D2 dissection. In addition to the ACTS-GC trial and CLASSIC trial (S-1 for 1 year and CAPOX for 6 months, respectively), two new regimens (DS and SOX for 6 months) are established standards of care for stage II and/r LN-positive gastric cancer.
Only 30% to 40% of patients with esophageal cancer have potentially resectable disease at presentation, and in many series, only 5% to 20% of those undergoing surgery alone for clinically localized disease are alive at 3 to 5 years.
Endoscopic therapy is most effective when used to treat small (<2 cm diameter), solitary, flat lesions that are confined to mucosa (T1a).
Surgery remains the best chance for durable survival for patients with locally advanced esophageal and gastroesophageal junction (GEJ) cancers.
Results of the CROSS trial also emphasized the beneficial role of chemoradiotherapy before surgery, which led to a significant increase in overall survival (OS) irrespective of tumor histology.
More than 60% of patients who present with newly diagnosed gastric, GEJ, and esophageal cancers will have advanced unresectable or metastatic disease. Although a cure is not possible, systemic therapy can prolong survival compared with best supportive care.
As of this writing, patients in the United States are likely to undergo frontline therapy with platinum-, fluoropyrimidine-, or taxane-based chemotherapy regimens, with the addition of trastuzumab in patients with HER2-positive disease.
Based on positive results from the RAINBOW trial, paclitaxel and ramucirumab (vascular endothelial growth factor receptor–2 targeted drug) is considered to be a standard for second-line treatment. Ramucirumab monotherapy is also considered a second-line option in advanced gastric cancer.
Pembrolizumab is currently approved for the treatment of metastatic squamous cell carcinoma (SCC) of the esophagus as second-line treatment for tumors with combined positive score (CPS) more than 10 and programmed cell death protein 1 (PD-L1)–positive advanced gastric cancer as third-line treatment in the US. Nivolumab is also approved in the US for metastatic SCC of the esophagus regardless of PD-L1 expression, and in Japan, South Korea, and Taiwan for the treatment of gastric cancer.
The Cancer Genome Atlas analysis has uncovered four genotypes of gastric cancer; however, it is not sufficient to change our treatment strategies, and additional work is needed.
A multimodality approach to therapy will be the cornerstone to screening, diagnosing, staging, treating, and supporting patients with upper gastrointestinal cancers.